To confirm the inhibitory effect of etidronate on the progression of vascular calcification (VC), 21 patients were randomly enrolled. All 21 patients had end-stage renal disease and were undergoing hemodialysis (HD) three times per week. Patients were observed clinically for 12 months before etidronate treatment and then etidronate was given orally just prior to sleep on the days of dialysis for 23 months. The aortic calcification area (ACA) increased significantly during the 12 months before etidronate treatment. While the ACA of the drug-treated group did not change 12 and 23 months after the initiation of etidronate treatment, the ACA in the control group was significantly elevated 23 months later. These results strongly indicate that etidronate inhibits the progression of VC. Bone mineral density did not change during etidronate treatment. Our findings suggest that etidronate might effectively protect against progressive VC in HD patients.